2-[N-(phenoxyacetyl)amino]-5-[2'-O-methyl-3',5'-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-β-D-ribofuranosyl]pyridine | 190907-88-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-[N-(phenoxyacetyl)amino]-5-[2'-O-methyl-3',5'-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-β-D-ribofuranosyl]pyridine
• 英文别名: N-[5-[(6aR,8S,9S,9aR)-9-methoxy-2,2,4,4-tetra(propan-2-yl)-6a,8,9,9a-tetrahydro-6H-furo[3,2-f][1,3,5,2,4]trioxadisilocin-8-yl]pyridin-2-yl]-2-phenoxyacetamide
• CAS: 190907-88-1
• 化学式: C₃₁H₄₈N₂O₇Si₂
• 分子量: 616.902
• InChiKey: WTKKGHOQUVVIGH-ZSEZPNIJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.51
• 重原子数：
  42
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  97.4
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-[N-(phenoxyacetyl)amino]-5-[2'-O-methyl-3',5'-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-β-D-ribofuranosyl]pyridine 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 以87%的产率得到2-[N-(phenoxyacetyl)amino]-5-(2'-O-methyl-β-D-ribofuranosyl)pyridine
  参考文献：
  名称：

  5-Substituted 2-Aminopyridine C-Nucleosides as Protonated Cytidine Equivalents:  Increasing Efficiency and Selectivity in DNA Triple-Helix Formation

  摘要：

  The easily accessible C-nucleoside 2-amino-5-(2'-deoxy-beta-D-ribofuranosyl)py (P) and its 3-methyl (P-Me) and 2'-O-methyl (P-OMe) derivatives were synthesized and incorporated as protonated cytidine equivalents in homopyrimidine oligodeoxynucleotides. T-m measurements indicate that oligonucleotides containing P or P-Me have a higher affinity to double-stranded DNA over the pH range of 6-8 than, 5-methylcytidine (C-Me) containing oligonucleotides. This increase in stability is most pronounced above pH 7.0. The average increase in T-m/modification for the dissociation of oligonucleotide d((TTTTTPTPTPTPTPT)-P-Me-P-Me-P-Me-P-Me-P-Me) from a 21-mer target duplex at pH 7.5 is 2.3 degrees C relative to oligonucleotide. d((TTTTTCTCTCTCTCT)-C-Me-C-Me-C-Me-C-Me-C-Me). The pH dependence and sequence composition effects are much less pronounced for P-Me (and also P) containing oligonucleotides than for C-Me containing ones. While oligonucleotide d((TTTCCCCTTTTCTTT)-C-Me-C-Me-C-Me-C-Me-C-Me) shows no longer any affinity to the target duplex above pH 6.5, oligonucleotide d((TTTPPPPTTTTPTTT)-P-Me-P-Me-P-Me-P-Me-P-Me) displays preserved binding with a T-m of 32.5 degrees C at pH 7.0 and even binds with a T-m of 23.3 degrees C at pH 8.0. Oligonucleotides containing P-OMe show distinctly less stable triple helices. The average decrease in T-m/modification for oligonucleotide d(TTTPTPOMeTPOMeTPOMeTPOMeTPOMeT) at pH 6.5 is 6.7 degrees C relative to the C-Me containing oligonucleotide. DNase I footprint titration experiments indicate that d((TTTTTPTPTPTPTPT)-P-Me-P-Me-P-Me-P-Me-P-Me) binds not only five times stronger to a 229 base pair DNA fragment than d((TTTTTCTCTCTCTCT)-C-Me-C-Me-C-Me-C-Me-C-Me) but also with higher selectivity; UV-melting experiments show that duplexes of d(TTTTTCTXTCTCTCT) (where X = P, P-Me, or P-OMe) With their antiparallel Watson-Crick complement are dramatically less stable (Delta T-m < -12 degrees C) at pH 8.0 than the corresponding natural duplex. Thus the new bases P and P-Me show Hoogsteen specific pairing behavior.

  DOI：

  10.1021/ja9704904
• 作为产物：
  描述：

  苯氧基乙酸酐 、 2-amino-5-[2'-O-methyl-3',5'-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-α,β-D-ribofuranosyl]pyridine 以 吡啶 为溶剂， 反应 5.0h， 以8%的产率得到2-[N-(phenoxyacetyl)amino]-5-[2'-O-methyl-3',5'-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-α-D-ribofuranosyl]pyridine
  参考文献：
  名称：

  5-Substituted 2-Aminopyridine C-Nucleosides as Protonated Cytidine Equivalents:  Increasing Efficiency and Selectivity in DNA Triple-Helix Formation

  摘要：

  The easily accessible C-nucleoside 2-amino-5-(2'-deoxy-beta-D-ribofuranosyl)py (P) and its 3-methyl (P-Me) and 2'-O-methyl (P-OMe) derivatives were synthesized and incorporated as protonated cytidine equivalents in homopyrimidine oligodeoxynucleotides. T-m measurements indicate that oligonucleotides containing P or P-Me have a higher affinity to double-stranded DNA over the pH range of 6-8 than, 5-methylcytidine (C-Me) containing oligonucleotides. This increase in stability is most pronounced above pH 7.0. The average increase in T-m/modification for the dissociation of oligonucleotide d((TTTTTPTPTPTPTPT)-P-Me-P-Me-P-Me-P-Me-P-Me) from a 21-mer target duplex at pH 7.5 is 2.3 degrees C relative to oligonucleotide. d((TTTTTCTCTCTCTCT)-C-Me-C-Me-C-Me-C-Me-C-Me). The pH dependence and sequence composition effects are much less pronounced for P-Me (and also P) containing oligonucleotides than for C-Me containing ones. While oligonucleotide d((TTTCCCCTTTTCTTT)-C-Me-C-Me-C-Me-C-Me-C-Me) shows no longer any affinity to the target duplex above pH 6.5, oligonucleotide d((TTTPPPPTTTTPTTT)-P-Me-P-Me-P-Me-P-Me-P-Me) displays preserved binding with a T-m of 32.5 degrees C at pH 7.0 and even binds with a T-m of 23.3 degrees C at pH 8.0. Oligonucleotides containing P-OMe show distinctly less stable triple helices. The average decrease in T-m/modification for oligonucleotide d(TTTPTPOMeTPOMeTPOMeTPOMeTPOMeT) at pH 6.5 is 6.7 degrees C relative to the C-Me containing oligonucleotide. DNase I footprint titration experiments indicate that d((TTTTTPTPTPTPTPT)-P-Me-P-Me-P-Me-P-Me-P-Me) binds not only five times stronger to a 229 base pair DNA fragment than d((TTTTTCTCTCTCTCT)-C-Me-C-Me-C-Me-C-Me-C-Me) but also with higher selectivity; UV-melting experiments show that duplexes of d(TTTTTCTXTCTCTCT) (where X = P, P-Me, or P-OMe) With their antiparallel Watson-Crick complement are dramatically less stable (Delta T-m < -12 degrees C) at pH 8.0 than the corresponding natural duplex. Thus the new bases P and P-Me show Hoogsteen specific pairing behavior.

  DOI：

  10.1021/ja9704904